Assessment
Treatment
Antipsychotic medications: available oral and short-acting intramuscular formulations*
Antipsychotic medications: relative side effects of oral formulations
Long-acting injectable antipsychotic medications: dosing*
Reversible inhibitors of human vesicular monoamine transporter type 2a
Medications for treatment of medication-induced parkinsonisma
Design and created by Guideline Central in participation with the American Psychiatric Association.
Treatment of Patients With Schizophrenia
American Psychiatric Association
Publication Date: October 27, 2020
Introduction
- The lifetime prevalence of schizophrenia is estimated to be approximately 0.7%. Worldwide, schizophrenia is one of the top 20 causes of disability.
- Schizophrenia is also associated with increased mortality, with a shortened lifespan and standardized mortality ratios that are reported to be twofold to fourfold those in the general population. Individuals often have physical health comorbidities such as cardiovascular, respiratory, and infectious diseases and malignancies, particularly lung cancer.
- About 4%–10% of persons with schizophrenia die by suicide, with rates that are highest among males in the early course of the disorder. Additional causes of death also include other unnatural events such as accidents and traumatic injuries.
- Harms from therapeutic interventions may include:
- adverse events that range from serious to less serious but affect tolerability to minor
- negative effects of the intervention on quality of life
- barriers and inconveniences associated with treatment
- other negative aspects of treatment that may influence decision-making by the patient, the clinician or both.
- The guideline statements should be implemented in the context of a person-centered treatment plan that includes evidence-based nonpharmacological and pharmacological treatments for schizophrenia.
- See full text guideline for additional information.
Assessment
Note: none of the subsequent statements are meant to stand alone.
As outlined in APA’s Practice Guidelines for the Psychiatric Evaluation of Adults (3rd edition), APA recommends that the initial assessment of a patient with a possible psychotic disorder include:
- the reason the individual is presenting for evaluation
- the patient’s goals and preferences for treatment
- a review of psychiatric symptoms and trauma history
- an assessment of tobacco and other substance use
- a psychiatric treatment history
- an assessment of physical health
- an assessment of psychosocial and cultural factors
- a mental status examination, including cognitive assessment
- an assessment of risk of suicide and aggressive behaviors.
APA recommends that the initial psychiatric evaluation of a patient with a possible psychotic disorder include a quantitative measure to identify and determine the severity of symptoms and impairments of functioning that may be a focus of treatment. ( 1, C )
APA recommends that patients with schizophrenia have a documented, comprehensive, and person-centered treatment plan that includes evidence-based nonpharmacological and pharmacological treatments. ( 1, C )
Figure 1. Managing Schizophrenia
Suggested physical and laboratory assessments for patients with schizophrenia
| Assessment | Initial or baselinea | Follow-upb |
|---|---|---|
| Assessments to monitor physical status and detect concomitant physical conditions | ||
| Vital signs | Pulse, blood pressure | Pulse, blood pressure, temperature as clinically indicated |
| Body weight and height | Body weight, height, BMI | BMI every visit for 6 months and at least quarterly thereafter |
| Hematology | CBC, including ANC | CBC, including ANC if clinically indicated (e.g., patients treated with clozapine) |
| Blood chemistries | Electrolytes, renal function tests, liver function tests, TSH | As clinically indicated |
| Pregnancy | Pregnancy test for women of childbearing potential | |
| Toxicology | Drug toxicology screen, if clinically indicated | Drug toxicology screen, if clinically indicated |
| Electrophysiological studies | EEG, if indicated on the basis of neurological exam or history | |
| Imaging | Brain imaging (CT or MRI, with MRI being preferred), if indicated on the basis of neurological exam or history | |
| Genetic testing | Chromosomal testing, if indicated on the basis of physical examination or history, including developmental historye | |
| Assessments related to other specific side effects of treatment | ||
| Diabetesf | Screening for diabetes risk factors,g fasting blood glucoseh | Fasting blood glucose or hemoglobin A1C at 4 months after initiating a new treatment and at least annually thereafterh |
| Hyperlipidemia | Lipid paneli | Lipid paneli at 4 months after initiating a new antipsychotic medication and at least annually thereafter |
| Metabolic syndrome | Determine whether metabolic syndrome criteria are metj | Determine whether metabolic syndrome criteria are metj at 4 months after initiating a new antipsychotic medication and at least annually thereafterj |
| QTc prolongation | ECG before treatment with chlorpromazine, droperidol, iloperidone, pimozide, thioridazine, or ziprasidonek or in the presence of cardiac risk factorsl | ECG with significant change in dose of chlorpromazine, droperidol, iloperidone, pimozide, thioridazine, or ziprasidone, or with the addition of other medications that can affect QTc interval in patients with cardiac risk factors or elevated baseline QTc intervals |
| Hyperprolactinemia | Screening for symptoms of hyperprolactinemiam Prolactin level, if indicated on the basis of clinical history | Screening for symptoms of hyperprolactinemia at each visit until stable, then yearly if treated with an antipsychotic known to increase prolactinm Prolactin level, if indicated on the basis of clinical history |
| Antipsychotic-induced movement disorders | Clinical assessment of akathisia, dystonia, parkinsonism, and other abnormal involuntary movements, including tardive dyskinesian Assessment with a structured instrument (e.g., AIMS, DISCUS) if such movements are present | Clinical assessment of akathisia, dystonia, parkinsonism, and other abnormal involuntary movements, including tardive dyskinesia, at each visitn Assessment with a structured instrument (e.g., AIMS, DISCUS) at a minimum of every 6 months in patients at high risk of tardive dyskinesia and at least every 12 months in other patientsp as well as if a new onset or exacerbation of preexisting movements is detected at any visit |
See full text guideline for additional important information in footnotes.
Treatment
Pharmacotherapy
APA recommends that patients with schizophrenia be treated with an antipsychotic medication and monitored for effectiveness and side effects.*
The choice of medication should consider:
- addressing patient's non- or partial response
- side-effect profile
- presence of other health conditions that may be affected by medication side effects
- formulations
- interactions and metabolism
- pharmacokinetic properties
See full text guideline for more information.
APA recommends that patients with schizophrenia whose symptoms have improved with an antipsychotic medication continue to be treated with an antipsychotic medication.* ( 1, A )
APA suggests that patients with schizophrenia whose symptoms have improved with an antipsychotic medication continue to be treated with the same antipsychotic medication.* ( 2, B )
APA recommends that patients with treatment-resistant schizophrenia be treated with clozapine.* ( 1, B )
APA recommends that patients with schizophrenia be treated with clozapine if the risk for suicide attempts or suicide remains substantial despite other treatments.* ( 1, B )
APA suggests that patients with schizophrenia be treated with clozapine if the risk for aggressive behavior remains substantial despite other treatments.* ( 2, C )
APA suggests that patients receive treatment with a long-acting injectable antipsychotic medication if they prefer such treatment or if they have a history of poor or uncertain adherence.* ( 2, B )
APA recommends that patients who have acute dystonia associated with antipsychotic therapy be treated with an anticholinergic medication. ( 1, C )
APA suggests the following options for patients who have parkinsonism associated with antipsychotic therapy: lowering the dosage of the antipsychotic medication, switching to another antipsychotic medication, or treating with an anticholinergic medication. ( 2, C )
APA suggests the following options for patients who have akathisia associated with antipsychotic therapy: lowering the dosage of the antipsychotic medication, switching to another antipsychotic medication, adding a benzodiazepine medication, or adding a beta-adrenergic-blocking agent. ( 2, C )
APA recommends that patients who have moderate to severe or disabling tardive dyskinesia associated with antipsychotic therapy be treated with a reversible inhibitor of the vesicular monoamine transporter 2 (VMAT2). ( 1, B )
Psychosocial Interventions
APA recommends that patients with schizophrenia who are experiencing a first episode of psychosis be treated in a coordinated specialty care program.* ( 1, B )
APA recommends that patients with schizophrenia be treated with cognitive-behavioral therapy for psychosis (CBTp).* ( 1, B )
APA recommends that patients with schizophrenia receive psychoeducation.* ( 1, B )
APA recommends that patients with schizophrenia receive supported employment services.* ( 1, B )
APA recommends that patients with schizophrenia receive assertive community treatment if there is a history of poor engagement with services leading to frequent relapse or social disruption (e.g., homelessness; legal difficulties, including imprisonment).* ( 1, B )
APA suggests that patients with schizophrenia who have ongoing contact with family receive family interventions.* ( 2, B )
APA suggests that patients with schizophrenia receive interventions aimed at developing self-management skills and enhancing person-oriented recovery.* ( 2, C )
APA suggests that patients with schizophrenia receive cognitive remediation.* ( 2, C )
APA suggests that patients with schizophrenia who have a therapeutic goal of enhanced social functioning receive social skills training.* ( 2, C )
APA suggests that patients with schizophrenia be treated with supportive psychotherapy.* ( 2, C )
* This guideline statement should be implemented in the context of a person-centered treatment plan that includes evidence-based nonpharmacological and pharmacological treatments for schizophrenia.
Antipsychotic medications: available oral and short-acting intramuscular formulations*
| Generic name Trade name (most common in U.S., may change) | Metabolic enzymes/ transporters | Available U.S. formulations (mg, unless otherwise noted) | Initial dose (mg/day) | Typical dose range (mg/day) | Maximum daily dose (mg/day) |
|---|---|---|---|---|---|
| First-generation antipsychotics | |||||
| Chlorpromazine Thorazine | CYP2D6 (Major), CYP1A2 (Minor), CYP3A4 (Minor) substrate | Tablet: 10, 25, 50, 100, 200 Short-acting injection (HCl): 25/mL (1 mL, 2 mL) | 25–100 | 200–800 | Oral: 1000–2000 |
| Fluphenazine Prolixin | CYP2D6 (Major) substrate | Tablet: 1, 2.5, 5, 10 Oral concentrate: 5/mL (120 mL) Elixir: 2.5/5 mL (60 mL) Short-acting injection (HCl): 2.5/mL (10 mL) | 2.5–10 | 6–20 | Oral: 40 IM: 10 |
| Haloperidol Haldol | CYP2D6 (Major), CYP3A4 (Major), CYP1A2 (Minor) substrate; 50-60% glucuronidation | Tablet: 0.5, 1, 2, 5, 10, 20 Oral concentrate: 2/mL (5 mL, 15 mL, 120 mL) Short-acting injection (lactate): 5/mL (1 mL, 10 mL) | 1–15 | 5–20 | Oral: 100 IM: 20 |
| Loxapine Loxitane | CYP1A2 (Minor), CYP2D6 (Minor), CYP3A4 (Minor) substrate; P-glycoprotein inhibitor | Capsule: 5, 10, 25, 50 Aerosol powder breath-activated inhalation: 10 | 20 | 60–100a | Oral: 250 Aerosol: 10 |
| Molindone Moban | CYP2D6 substrate | Tablet: 5, 10, 25 | 50–75 | 30–100a | 225 |
| Perphenazine Trilafon | CYP2D6 (Major), CYP1A2 (Minor), CYP2C19 (Minor), CYP2C9 (Minor), CYP3A4 (Minor) substrate | Tablet: 2, 4, 8, 16 | 8–16 | 8–32 | 64 |
| Pimozide Orap | CYP1A2 (Major), CYP2D6 (Major), CYP3A4 (Major) substrate | Tablet: 1, 2 | 0.5–2 | 2–4 | 10 |
| Thioridazine Mellaril | CYP2D6 (Major) substrate and moderate inhibitor, CYP2C19 (Minor) substrate | Tablet: 10, 25, 50, 100 | 150–300 | 300–800a | 800 |
| Thiothixene Navane | CYP1A2 (Major) substrate | Capsule: 1, 2, 5, 10 | 6–10 | 15–30 | 60 |
| Trifluoperazine Stelazine | CYP1A2 (Major) substrate | Tablet: 1, 2, 5, 10 | 4–10 | 15–20 | 50 |
| Second-generation antipsychotics | |||||
| Aripiprazole Abilify | CYP2D6 (Major), CYP3A4 (Major) substrate | Tablet: 2, 5, 10, 15, 20, 30 Tablet, disintegrating: 10, 15 Tablet with ingestible event marker (Mycite): 2, 5, 10, 15, 20, 30 Solution: 1/mL (150 mL) | 10–15 | 10–15 | 30 |
| Asenapine Saphris | CYP1A2 (Major), CYP2D6 (Minor), CYP3A4 (Minor) substrate; glucuronidation by UGT1A4; CYP2D6 weak inhibitor | Tablet, sublingual: 2.5, 5, 10 | 10 | 20 | 20 |
| Asenapine Secuado | CYP1A2 (Major), CYP2D6 (Minor), CYP3A4 (Minor) substrate; glucuronidation by UGT1A4; CYP2D6 weak inhibitor | Transdermal system: 3.8 mg/24 hours, 5.7 mg/24 hours, 7.6 mg/24 hours | 3.8 | 3.8–7.6 | 7.6 |
| Brexpiprazole Rexulti | CYP3A4 (Major), CYP2D6 (Major) substrate | Tablet: 0.25, 0.5, 1, 2, 3, 4 | 1 | 2–4 | 4 |
| Cariprazine Vraylar | CYP3A4 (Major), CYP2D6 (Minor) substrate | Capsule: 1.5, 3, 4.5, 6 | 1.5 | 1.5–6 | 6b |
| Clozapinec Clozaril, FazaClo, Versacloz | CYP1A2 (Major), CYP2A6 (Minor), CYP2C19 (Minor), CYP2C9 (Minor), CYP2D6 (Minor), CYP3A4 (Minor) substrate | Tablet: 25, 50, 100, 200 Tablet, disintegrating: 12.5, 25, 100, 150, 200 Oral suspension: 50/mL (100 mL) | 12.5–25 | 300–450d | 900 |
| Iloperidone Fanapt | CYP2D6 (Major), CYP3A4 (Minor) substrate, CYP3A4 weak inhibitor | Tablet: 1, 2, 4, 6, 8, 10, 12 | 2 | 12–24 | 24 |
| Lurasidone Latuda | CYP3A4 (Major) substrate, CYP3A4 weak inhibitor | Tablet: 20, 40, 60, 80, 120 | 40 | 40–120 | 160 |
| Olanzapine Zyprexa | CYP1A2 (Major), CYP2D6 (Minor) substrate; metabolized via direct glucuronidation | Tablet: 2.5, 5, 7.5, 10, 15, 20 Tablet, disintegrating: 5, 10, 15, 20 Short-acting IM powder for solution: 10/2 mL | 5–10 | 10–20 | 20e |
| Paliperidone Invega | P-glycoprotein/ ABCB1, CYP2D6 (Minor), CYP3A4 (Minor) substrate | Tablet, extended release: 1.5, 3, 6, 9 | 6 | 3–12 | 12 |
| Quetiapine Seroquel | CYP3A4 (Major), CYP2D6 (Minor) substrate | Tablet, immediate release: 25, 50, 100, 200, 300, 400 Tablet, extended release: 50, 150, 200, 300, 400 | Immediate release: 50 Extended release: 300 | 400–800 | 800 |
| Risperidone Risperdal | CYP2D6 (Major), CYP3A4 (Minor), P-glycoprotein/ ABCB1 substrate, N-dealkylation (minor), CYP2D6 weak inhibitor | Tablet: 0.25, 0.5, 1, 2, 3, 4 Tablet, disintegrating: 0.25, 0.5, 1, 2, 3, 4 Oral solution: 1/mL (30 mL) | 2 | 2–8 | 8f |
| Ziprasidone Geodon | CYP1A2 (Minor), CYP3A4 (Minor) substrate, glutathione, aldehyde oxidase | Capsule: 20, 40, 60, 80 Solution reconstituted, IM: 20 | 40 | 80–160 | 320 |
* This table includes information compiled from multiple sources. Detailed information on such issues as dose regimen, dose adjustments, medication administration procedures, handling precautions, and storage can be found in product labeling. It is recommended that readers consult product labeling information for authoritative information on these medications.
a Usually given in divided doses.
b Up to 9 mg/day has been studied in clinical trials.
Clozapine levels should be drawn after at least 3 days on a stable dose and about 12 hours after the last dose. Levels associated with efficacy show individual variation, but efficacy typically begins at a level above 250 ng/mL, with the most efficacy seen at levels higher than 350 ng/mL. U.S. prescribers must complete Clozapine REMS education (https://www.clozapinerems.com/ ) and follow requirements for a baseline CBC and ANC, and for ANC monitoring before and during treatment. Refer to clozapine labeling for detailed instructions on dose titration and dose adjustments with CYP450 interactions.
d May be taken without regard to food or other medications unless specifically noted.
e Olanzapine has been used at higher dosages, typically up to 30 mg/day, although some case series describe use of up to 60 mg/day.
f Dosages of risperidone up to 16 mg/day have been studied in clinical trials. However, doses >6 mg for twice-daily dosing do not appear to confer additional benefit and have a higher incidence of extrapyramidal symptoms than do lower doses.
a Usually given in divided doses.
b Up to 9 mg/day has been studied in clinical trials.
Clozapine levels should be drawn after at least 3 days on a stable dose and about 12 hours after the last dose. Levels associated with efficacy show individual variation, but efficacy typically begins at a level above 250 ng/mL, with the most efficacy seen at levels higher than 350 ng/mL. U.S. prescribers must complete Clozapine REMS education (https://www.clozapinerems.com/ ) and follow requirements for a baseline CBC and ANC, and for ANC monitoring before and during treatment. Refer to clozapine labeling for detailed instructions on dose titration and dose adjustments with CYP450 interactions.
d May be taken without regard to food or other medications unless specifically noted.
e Olanzapine has been used at higher dosages, typically up to 30 mg/day, although some case series describe use of up to 60 mg/day.
f Dosages of risperidone up to 16 mg/day have been studied in clinical trials. However, doses >6 mg for twice-daily dosing do not appear to confer additional benefit and have a higher incidence of extrapyramidal symptoms than do lower doses.
Antipsychotic medications: relative side effects of oral formulations
| Generic name | Akathisia | Parkinsonism | Dystonia | Tardive dyskinesia |
|---|---|---|---|---|
| First-generation antipsychotics | ||||
| Chlorpromazine | ++ | ++ | ++ | +++ |
| Fluphenazine | +++ | +++ | +++ | +++ |
| Haloperidol | +++ | +++ | +++ | +++ |
| Loxapine | ++ | ++ | ++ | ++ |
| Molindone | ++ | ++ | ++ | ++ |
| Perphenazine | ++ | ++ | ++ | ++ |
| Pimozide | +++ | +++ | ++ | +++ |
| Thioridazine | + | + | + | + |
| Thiothixene | +++ | +++ | +++ | +++ |
| Trifluoperazine | ++ | ++ | ++ | ++ |
| Second-generation antipsychotics | ||||
| Aripiprazole | ++ | + | + | + |
| Asenapine | ++ | + | ++ | ++ |
| Brexpiprazole | ++ | + | + | + |
| Cariprazine | ++ | + | + | + |
| Clozapine | + | + | + | + |
| Iloperidone | + | + | + | + |
| Lurasidone | ++ | ++ | ++ | ++ |
| Olanzapine | ++ | ++ | + | + |
| Paliperidone | ++ | ++ | ++ | ++ |
| Quetiapine | + | + | + | + |
| Risperidone | ++ | ++ | ++ | ++ |
| Ziprasidone | ++ | + | + | + |
| Generic name | Hyperprolactinemia a | Anticholinergic | Sedation |
|---|---|---|---|
| First-generation antipsychotics | |||
| Chlorpromazine | + | +++ | +++ |
| Fluphenazine | +++ | + | + |
| Haloperidol | +++ | + | + |
| Loxapine | ++ | ++ | ++ |
| Molindone | ++ | + | ++ |
| Perphenazine | ++ | ++ | ++ |
| Pimozide | +++ | + | + |
| Thioridazine | ++ | +++ | +++ |
| Thiothixene | +++ | + | + |
| Trifluoperazine | ++ | ++ | + |
| Second-generation antipsychotics | |||
| Aripiprazole | + | + | + |
| Asenapine | ++ | + | ++ |
| Brexpiprazole | + | + | ++ |
| Cariprazine | + | ++ | ++ |
| Clozapine | + | +++ | +++ |
| Iloperidone | ++ | + | ++ |
| Lurasidone | + | + | ++ |
| Olanzapine | ++ | ++ | +++ |
| Paliperidone | +++ | + | + |
| Quetiapine | + | ++ | +++ |
| Risperidone | +++ | + | ++ |
| Ziprasidone | ++ | + | ++ |
| Generic name | Seizures | Orthostasis | QT prolongation | Weight gain |
|---|---|---|---|---|
| First-generation antipsychotics | ||||
| Chlorpromazine | ++ | +++ | +++ | ++ |
| Fluphenazine | + | + | ++ | ++ |
| Haloperidol | + | + | ++ | ++ |
| Loxapine | + | ++ | ++ | + |
| Molindone | + | + | ++ | + |
| Perphenazine | + | ++ | ++ | ++ |
| Pimozide | +++ | + | +++ | + |
| Thioridazine | ++ | +++ | +++ | ++ |
| Thiothixene | +++ | + | ++ | + |
| Trifluoperazine | + | + | ++ | ++ |
| Second-generation antipsychotics | ||||
| Aripiprazole | + | + | + | + |
| Asenapine | + | ++ | ++ | ++ |
| Brexpiprazole | + | + | ++ | + |
| Cariprazine | + | + | ++ | ++ |
| Clozapine | +++ | +++ | ++ | +++ |
| Iloperidone | + | +++ | +++ | ++ |
| Lurasidone | + | + | + | + |
| Olanzapine | ++ | ++ | ++ | +++ |
| Paliperidone | + | ++ | ++ | ++ |
| Quetiapine | ++ | ++ | ++ | ++ |
| Risperidone | + | ++ | ++ | ++ |
| Ziprasidone | + | ++ | +++ | + |
| Generic name | Hyperlipidemia | Glucose abnormalities | Comments |
|---|---|---|---|
| First-generation antipsychotics | |||
| Chlorpromazine | + | ++ | |
| Fluphenazine | + | + | |
| Haloperidol | + | + | |
| Loxapine | + | + | |
| Molindone | + | + | |
| Perphenazine | + | + | |
| Pimozide | + | + | |
| Thioridazine | + | + | b |
| Thiothixene | + | + | |
| Trifluoperazine | + | + | |
| Second-generation antipsychotics | |||
| Aripiprazole | + | + | c |
| Asenapine | ++ | ++ | d |
| Brexpiprazole | ++ | + | |
| Cariprazine | + | + | |
| Clozapine | +++ | +++ | e |
| Iloperidone | + | ++ | |
| Lurasidone | ++ | ++ | f |
| Olanzapine | +++ | +++ | |
| Paliperidone | ++ | + | |
| Quetiapine | +++ | ++ | |
| Risperidone | + | ++ | g |
| Ziprasidone | + | + | |
+=seldom; ++=sometimes; +++=often
a In general, rates of sexual dysfunction parallel rates of hyperprolactinemia except where noted in comments.
Pigmentary retinopathy; high rates of sexual dysfunction; avoid use if QTc interval is >450 msec or with concomitant use of drugs that prolong the QTc interval or inhibit CYP2D6
c FDA safety alert for impulse control disorders (e.g., gambling, binge eating); may reduce hyperprolactinemia with other antipsychotics
d Oral hypoesthesia
e Increased salivation common; high rate of sexual dysfunction; severe constipation and paralytic ileus possible; fever can occur with initiation; myocarditis is infrequent; cardiomyopathy and severe neutropenia are rare
f Dose-related creatinine increase in some patients
g Intraoperative floppy iris syndrome reported
a In general, rates of sexual dysfunction parallel rates of hyperprolactinemia except where noted in comments.
Pigmentary retinopathy; high rates of sexual dysfunction; avoid use if QTc interval is >450 msec or with concomitant use of drugs that prolong the QTc interval or inhibit CYP2D6
c FDA safety alert for impulse control disorders (e.g., gambling, binge eating); may reduce hyperprolactinemia with other antipsychotics
d Oral hypoesthesia
e Increased salivation common; high rate of sexual dysfunction; severe constipation and paralytic ileus possible; fever can occur with initiation; myocarditis is infrequent; cardiomyopathy and severe neutropenia are rare
f Dose-related creatinine increase in some patients
g Intraoperative floppy iris syndrome reported
Long-acting injectable antipsychotic medications: dosing*
| Generic name | Trade name | Dose conversions | Initial dose (mg) | Typical dose(mg) | Maximum dose(mg) | Dosing frequency | Need for initial oral supplementation |
|---|---|---|---|---|---|---|---|
| First-generation antipsychotics | |||||||
| Fluphenazine | Prolixin Decanoate | For each 10 mg/day oral, give 12.5 mg decanoate every 3 weeks | 6.25–25 every 2 weeks | 6.25–25 every 2–4 weeks | 100 | 2–4 weeks | Decrease oral dose by half after first injection, then discontinue with second injection |
| Haloperidol | Haldol decanoate | For each 5 mg/day oral, give 50–75 mg decanoate every 4 weeks | Determined by oral dose and/or risk of relapse up to a maximum of 100 mg | 50–200 (10–15 times previous oral dose) | 450/month | 4 weeks | Taper and discontinue after two to three injections |
| Second-generation antipsychotics | |||||||
| Aripiprazole monohydrate | Abilify Maintena | Not applicable | 400 | 400 | 400/month | Monthly | Continue oral for 14 days after initial injection |
| Aripiprazole lauroxil | Aristada Initio | Not applicable | 675 | 675 | 675 | Single dose to initiate Aristada treatment or reinitiate treatment after a missed Aristada dose. Not for repeated dosing. | Must be administered in conjunction with one 30 mg dose of oral aripiprazole. |
| Aripiprazole lauroxil | Aristada | 10 mg/day orally, give 441 mg IM/month 15 mg/day orally, give 662 mg/month IM, 882 mg IM every 6 weeks, or 1,064 mg IM every 2 months 20 mg/day or greater orally, give 882 mg/ month IM | Monthly: 441, 662, 882 Every 6 weeks: 882 Every 2 months: 1,064 | Monthly: 441, 662, 882 Every 6 weeks: 882 Every 2 months: 1,064 | 882/month | Monthly: 441, 662, 882 Every 6 weeks: 882 Every 2 months: 1,064 | There are two ways to initiate treatment: 1. Give one IM injection of Aristada Initio 675 mg and one dose of oral aripiprazole 30 mg, or 2. Give 21 days of oral aripiprazole in conjunction with the first Aristada injection |
| Olanzapine | Zyprexa Relprevv | 10 mg/day orally, 210 mg every 2 weeks for four doses, or 405 mg every 4 weeks 15 mg/day orally, 300 mg every 2 weeks for four doses 20 mg/day orally, 300 mg every 2 weeks | Determined by oral dose | 150 mg, 210 mg, or 300 mg every 2 weeks or 300 mg or 405 mg every 4 weeks | 300 mg every 2 weeks or 405 mg every 4 weeks | 2–4 weeks | Not required |
| Paliperidone palmitate | Invega Sustenna | 3 mg oral paliperidone, give 39–78 mg IM 6 mg oral, give 117 mg IM 9 mg, oral give 156 mg IM 12 mg oral, give 234 mg IM | 234 mg IM on day 1 and 156 mg IM 1 week later, both administered in the deltoid muscle | 78–234 mg monthly beginning at week 5 | 234 mg/ month | Monthly | Not required |
| Paliperidone palmitate | Invega Trinza | Conversion from monthly Invega Sustenna to every 3-month injections of Invega Trinza: 78 mg, give 273 mg 117 mg, give 410 mg 156 mg, give 546 mg 234 mg, give 819 mg | Dependent on last dose of monthly paliperidone | 273–819 | 819/3 months | Every 3 months | Not applicable |
| Risperidone | Risperdal Consta | Oral risperidone to Risperidone Consta IM: ≤3 mg/day, give 25 mg/2 weeks >3 to ≤5 mg/day, give 37.5 mg/2 weeks >5 mg/day, give 50 mg/2 weeks | 25 every 2 weeks | 25–50 every 2 weeks | 50 every 2 weeks | 2 weeks | Continue oral for 3 weeks (21 days) |
| Risperidone | Perseris | Oral risperidone to subcutaneous risperidone extended release: 3 mg/day, give 90 mg/monthly 4 mg/day, give 120 mg/monthly | Determined by oral dose | 90–120 monthly | 120/month | Monthly | Neither a loading dose nor oral overlap is needed |
* This table includes information compiled from multiple sources. Detailed information on such issues as dose regimen, dose adjustments, medication administration procedures, handling precautions, and storage can be found in product labeling. It is recommended that readers consult product labeling information for authoritative information on these medications.
Reversible inhibitors of human vesicular monoamine transporter type 2a
| Reversible inhibitors of human vesicular monoamine transporter type 2a | |||
| Genric name | Deutetrabenazine | Tetrabenazine | Valbenazine |
| Trade name | Austedo | Xenazine | Ingrezza |
| Available formulations (mg) | Tablet: 6, 9, 12 | Tablet: 12.5, 25 | Capsule: 40, 80 |
| Typical dose range (mg/day) | 12–48 | 25–75 | 40–80 |
| Bioavailability | 80% | 75% | 49% |
| Time to peak level (hours) | 3–4 | 1–2 | 0.5–1 |
| Protein binding | 60% to 68% (alpha-HTBZ) 59% to 63% (beta-HTBZ) | 82% to 85% 60% to 68% (alpha-HTBZ) 59% to 63% (beta-HTBZ) | >99% 64% alpha-HTBZ |
| Metabolism | Hepatic | Hepatic | Hepatic |
| Metabolic enzymes/ transporters | Major substrate of CYP2D6, minor substrate of CYP1A2 and CYP3A4 | Major substrate of CYP2D6 | Major substrate of CYP3A4, minor substrate of CYP2D6 |
| Metabolites | Deuterated alpha and beta HTBZ: Active | Alpha, beta and O-dealkylated HTBZ: Active | alpha- HTBZ: Active |
| Elimination half-life (hours) | Deuterated alpha and beta HTBZ: 9–10 | Alpha-HTBZ: 4–8 Beta-HTBZ: 2–4 | 15-22 |
| Excretion | Urine (~75%-85% changed); feces (~8%–11%) | Urine (~75% changed); feces (~7%–16%) | Urine: 60%; feces: 30% |
| Hepatic impairment | Contraindicated | Contraindicated | Maximum dose of 40 mg daily with moderate to severe impairment (Child-Pugh score 7–15) |
| Renal impairment | No information available | No information available | Use not recommended in severe renal impairment (CrCl <30 mL/min) |
| Common adverse effect | Sedation | Sedation, depression, extrapyramidal effects, insomnia, akathisia, anxiety, nausea, falls | Sedation |
| Effect of food on bioavailability | Food effects maximal concentration. Administer with food. Swallow tablets whole and do not chew, crush, or break. | Unaffected by food | Can be taken with or without food. High fat meals decreased the Cmax and AUC for valbenazine but values for the active metabolite (alpha-HTBZ) are unchanged |
a This table includes information compiled from multiple sources. Detailed information on issues such as dose regimen, dose adjustments, medication administration procedures, handling precautions, and storage can be found in product labeling. It is recommended that readers consult product labeling information for authoritative information on these medications.
Medications for treatment of medication-induced parkinsonisma
| Medications for treatment of medication-induced parkinsonisma | ||||
| Genric name | Amantadine | Benztropine mesylate | Diphenhydramine | Trihexyphenidyl hydrochloride |
| Trade name | Symmetrel | Cogentin | Benadryl | Artane |
| Mechanism of action | Uncompetitive NMDA receptor antagonist (weak) | Muscarinic antagonist | Histamine H1 antagonist | Muscarinic antagonist |
| Available formulations (mg, unless otherwise noted) | Tablet: 100 Tablet, extended release: 129, 193, 258 Capsule: 100 Capsule, liquid filled: 100 Capsule, extended release: 68.5, 137 Oral syrup: 50/5 mL | Tablet: 0.5, 1, 2 Solution, injection: 1/mL (2 mL) | Capsule: 25, 50 Oral elixir: 12.5/5 mL Oral solution: 12.5/5 mL, 6.25/1 mL Tablet: 25, 50 Solution, injection: 50/1 mL Other brand name formulations are available for allergy relief | Oral elixir: 0.4/mL (473 mL) Tablet: 2, 5 |
| Typical dose range (mg/day) | Immediate release tablet or capsule: 100–300 Extended release tablet: 129–322 | Tablet: 0.5–6.0 Solution, injection: 1–2 | Oral: 75–200 Solution, injection: 10–50 | Oral: 5–15 |
| Bioavailability | 86%–94% | 29% | 40%–70% | 100% |
| Time to peak level (hours) | Immediate release: 2–4 Extended release: 7.5–12 | Oral: 7 IM: minutes | 1–4 | 1.3 |
| Protein binding | 67% | 95% | 76%–85% | Not known |
| Metabolism | Primarily renal | Hepatic | Hepatic | Not known |
| Metabolic enzymes/ transporters | Substrate of organic cation transporter 2 | Substrate of CYP2D6 (minor) | Extensively hepatic N-demethylation via CYP2D6; minor demethylation via CYP1A2, CYP2C9 and CYP2C19; inhibits CYP2D6 (weak) | None known |
| Metabolites | Multiple; unknown activity | Not known | Inactive | Not known |
| Elimination half-life (hours) | 16–17 | 7 | 4–8 | 4 |
| Excretion | Urine 85% unchanged; 0.6% fecal | Urine | Urine (as metabolites and unchanged drug) | Urine and bile |
| Hepatic impairment | No dose adjustments noted in labeling | No dose adjustments noted in labeling | No dose adjustments noted in labeling | No dose adjustments noted in labeling |
| Renal impairment | Elimination half-life increases with renal impairment | No dose adjustments noted in labeling | No dose adjustments noted in labeling. However, dosing interval may need to be increased or dosage reduced in older individuals and those with renal impairments. | No dose adjustments noted in labeling |
| Comments | Negligible removal by dialysis; do not crush or divide extended release products | Onset of action with IV dose is comparable to IM | Total daily dose typically divided into 3–4 doses per day. Maximum daily dose 300 mg for oral and 400 mg for IM/IV, with 100 mg maximum dose for IV/IM. Give IV dose at a rate of 25 mg/minute. Give IM dose by deep intramuscular injection because subcutaneous or intradermal injection can cause necrosis. | |
a This table includes information compiled from multiple sources. Detailed information on such issues as dose regimen, dose adjustments, medication administration procedures, handling precautions, and storage can be found in product labeling. It is recommended that readers consult product labeling information for authoritative information on these medications.
Grading Recommendations
| Grade | Description |
| 1 | Recommendation: indicates confidence that the benefits of the intervention clearly outweigh harms. |
| 2 | Suggestion: indicates greater uncertainty: although the benefits of the statement are still viewed as outweighing the harms, balance of benefits and harms is more difficult to judge, or the benefits or the harms may be less clear. With a suggestion, patient values and preferences may be more variable, and this can influence the clinical decision that is ultimately made. |
| Grade | Strength of Evidence |
| A | High: high confidence that the evidence reflects the true effect. Further research is very unlikely to change our confidence in the estimate of effect. |
| B | Moderate: moderate confidence that the evidence reflects the true effect. Further research may change our confidence in the estimate of effect and may change the estimate. |
| C | Low: low confidence that the evidence reflects the true effect. Further research is likely to change our confidence in the estimate of effect and is likely to change the estimate. |
Abbreviations
- AIMS
- abnormal involuntary movement scale
- ANC
- absolute neutrophil count
- AUC
- area under the curve
- BMI
- body mass index (kg/m2)
- CBC
- complete blood cell count
- CBTp
- cognitive-behavioral therapy for psychosis
- Cmax
- maximum plasma concentration
- CT
- computed tomography
- CYP
- cytochrome P450
- DISCUS
- Dyskinesia Identification System-Condensed User Scale
- EEG
- electroencephalogram
- HCI
- hydrochloride
- HTBZ
- dihydrotetrabenazine
- IM
- intramuscular
- IV
- intravenous
- LAI
- long -acting injectable
- MRI
- magnetic resonance imaging
- NMDA
- N-methyl-D-aspartate
- QTc
- corrected QT interval
- REMS
- risk evaluation and mitigation strategy
- TSH
- thyroid stimulating hormone
- VMAT2
- vesicular monoamine transporter 2
Source Citation
American Psychiatric Association: Practice Guideline for the Treatment of Patients With Schizophrenia, 3rd Edition. Washington, DC, American Psychiatric Publishing, 2021
Disclaimer
This resource is for informational purposes only, intended as a quick-reference tool based on the cited source guideline(s), and should not be used as a substitute for the independent professional judgment of healthcare providers. Practice guidelines are unable to account for every individual variation among patients or take the place of clinician judgment, and the ultimate decision concerning the propriety of any course of conduct must be made by healthcare providers after consideration of each individual patient situation. Guideline Central does not endorse any specific guideline(s) or guideline recommendations and has not independently verified the accuracy hereof. Any use of this resource or any other Guideline Central resources is strictly voluntary.
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